SCI Consortium Study: Neural Stem Cell Transplantation for Cervical Spinal Cord Injury

脊髓损伤(SCI)往往损害，不仅是白质轴索束的信号传输到和 来自大脑，也包括中央灰质，导致中间神经元和运动神经元节段性丢失 神经元。神经干细胞(NSCs)移植有可能取代丢失的神经元和 神经胶质细胞。这些移植的神经元可以在断开连接的脊髓节段之间形成功能继电器。 由伤势所致。我们已经产生了具有脊髓特征的人类神经干细胞，以检验这一假设 脊髓神经干细胞将更合适地整合到损伤脊髓的部位。我们的 初步数据提供证据表明，大鼠和人类的神经干细胞都可以移植到 多种脊髓损伤模型，包括临床相关的挫伤模型。然而，人类神经干细胞 似乎在更长的时间线上发展，更类似于人类的发展。因此，我们的目标是 鉴定人脊髓神经干细胞(ScNSCs)的成熟和表型。长期研究 将在临床上评估这种scNSC疗法的有效性、安全性和突触整合 相关颈髓挫伤模型的建立。 这项工作具有很高的创新性和临床导向： 1)我们将使用最适用于人类脊髓损伤的挫伤类型。 2)我们将研究一种新的具有脊髓特征的人类神经干细胞系(ScNSCs)。 3)长期研究将检验我们的主导细胞--单细胞神经干细胞的成熟度、有效性和安全性。 候选，用于治疗脊髓损伤。 4)新的跨突触追踪技术将被用来评估两个宿主的突触整合 移植物的输入和移植物输出到宿主运动神经元。

Spinal cord injury (SCI) often damages, not only white matter axon tracts that transmits signals to and from the brain, but also the central gray matter, causing segmental loss of interneurons and motor neurons. Transplantation of neural stem cells (NSCs) has the potential to replace lost neurons and glia. These transplanted neurons can form functional relays between spinal segments disconnected by the injury. We have generated human NSCs with a spinal cord identity to test the hypothesis that spinal cord NSCs will more appropriately integrate into sites of the injured spinal cord. Our preliminary data provide evidence that both rat and human neural stem cells can be transplanted into multiple models of SCI, including a clinically relevant contusion model. However, humans NSCs appear to develop on a longer timeline, more similar to human development. Therefore, we aim to characterize the maturation and phenotype of human spinal cord NSCs (scNSCs). Long-term studies will assess the efficacy, safety and synaptic integration of such scNSC therapy in a clinically relevant contusive model of cervical SCI. This work is highly innovative and clinically oriented: 1) We will utilize a contusion type injury that is most applicable to human SCI. 2) We will examine a novel human NSC line with a spinal cord identity (scNSCs). 3) Long-term studies will examine the maturation, efficacy and safety of scNSCs, our lead cell candidate, for the treatment of spinal cord injury. 4) Novel trans-synaptic tracing techniques will be used to assess the synaptic integration of both host inputs to the graft and graft outputs to host motor neurons.